The broad long term objective of this research is to develop new strategies in diagnostic and biomedical imaging based on early transition metal cluster compounds of high atomic number elements. This research is motivated by the nonideal radiological properties and toxic side effects of currently used iodinated contrast agents.
The specific aims of this project are to develop ligand encapsulation strategies for hexanuclear early transition metal clusters, to characterize the resulting cluster coordination complexes, and to determine their physicochemical, cytotoxicological, and X-ray attenuation properties. The goal is to develop a new paradigm in diagnostic, structural, and functional imaging based on high atomic number transition metal clusters with enhanced photoelectric scattering of incident X-rays. This approach permits the use of higher energy X-rays which lowers the absorbed patient dose while multiplying the X-ray attenuation normally observed with iodinated contrast agents. Hexanuclear clusters with new multidentate ligands, designed by molecular modelling methods, will be synthesized and characterized by spectroscopic and structural methods. The aqueous solubilities and stabilities, solution osmolalities, solution viscosities, and partition coefficients will then be determined. The cytotoxicities of the cluster compounds in cell viability and cell proliferation will be assayed by tissue culture methods. The single wavelength and polychromatic X-ray attenuations of aqueous solution phantoms will be measured by use of radioisotopes and a clinical CT scanner. The proposed science is an innovative combination of contemporary inorganic cluster chemistry and diagnostic radiology. The results are not only applicable to the development of new clinical contrast agents but also to the development of agents for targeted radiotherapy and structural/functional imaging.
